Investigation of G007-LK treatment in mouse and human melanoma cell lines

Group - 24

Introduction

  • WNT/β-catenin pathway -> disregulation in melanoma

  • G007LK -> decreases WNT/β-catenin signaling

  • Two data sets and two metadata sets (mouse and human)

  • Goal was to identify up and down regulated genes after G007LK treatment

Methods

Cleaning

  • How we cleaned the data and why

Augmentation

  • How we processed or data to prepare it for analysis
  • Why we did 0 handling and how
  • Why we did log2 fold expressions

Description

  • Observed major zero expression levels through cell lines in each of treatment

Description

Results

Mouse gene expression analysis

  • Only 346 significantly regulated genes out of 39075
  • 0 handling making estimated treatment impact on expressions unsure.

Analysis of regulated Mouse genes across the 3 treatments

  • Approximately equal amounts of significantly regulated genes in each treatment

  • However, the overlap is very small

Discussion

The Human Analysis

  • PCA.1 The way the cell lines are segregated highlight the biological background outweighs the direct impact of the treatment in regards to gene expression variance

  • PCA.2 Outliers like SkMEL28 and A375, along with the distinctive positioning of WM852, suggested unique gene expression profiles potentially associated with the response to G007.LK.

  • This limitation in explaining variance by the principal components underscores the complex nature of gene expression changes in the human cell lines.

Discussion

  • In our mouse model, the BVES gene appears to be the most significantly impacted.This gene contributes to regeneration processes

  • This transition between species allowed us to explore cross-species insights in regards to the effect of the G007.LK compound

  • More extensive work is needed to fully understand the impact of the G007.LK in gene expression and cellular pathway across different melanoma cells

References

  • Jo Waaler (2022) Human melanoma cell lines treated with G007-LK. BioStudies, E-MTAB-8438. Retrieved from https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-8438

  • Jo Waaler (2021). Mouse melanoma cell line B16-F10 treated with G007-LK. BioStudies, E-MTAB-8101. Retrieved from https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-8101

  • Waaler, Jo, et al. “Tankyrase Inhibition Sensitizes Melanoma to PD-1 Immune Checkpoint Blockade in Syngeneic Mouse Models.” Communications Biology, vol. 3, no. 1, 24 Apr. 2020, https://doi.org/10.1038%2Fs42003-020-0916-2 Accessed 25 Nov. 2023

  • Martín‐Fernández, Josep Antoni, Javier Palarea‐Albaladejo, and Ricardo Antonio Olea. “Dealing with zeros.” Compositional data analysis: Theory and applications (2011): 43-58.